阿米什人群中阿尔茨海默病相关血浆生物标志物的遗传力。

Heritability of Alzheimer-related plasma biomarkers in the Amish population.

作者信息

Wang Ping, Song Yeunjoo E, Lynn Audrey, Miskimen Kristy, Gulyayev Alex, Prough Michael B, Dorfsman Daniel A, Laux Renee A, Fuzzell Sarada L, Hochstetler Sherri D, Zaman Andrew F, Adams Larry D, Caywood Laura J, Clouse Jason E, Herington Sharlene D, Whitehead Patrice, Liu Yining, Moore Noel, Ogrocki Paula, Lerner Alan J, Griswold Anthony J, Vance Jeffery M, Cuccaro Michael L, Scott William K, Pericak-Vance Margaret A, Haines Jonathan L

机构信息

Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA.

Cleveland Institute for Computational Biology, 2103 Cornell Road, Cleveland, OH 44106, USA.

出版信息

medRxiv. 2025 May 21:2025.05.13.25327557. doi: 10.1101/2025.05.13.25327557.

DOI:10.1101/2025.05.13.25327557

PMID:40463532

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12132146/

Abstract

INTRODUCTION

Plasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored.

METHODS

We measured plasma amyloid beta 40 (Aβ40), Aβ42, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau181), Aβ42/t-tau, Aβ42/p-tau181, neurofilament light chain, and glial fibrillary acidic protein in the Midwestern Amish. Pedigree-based heritability was estimated from multigenerational pedigrees, and SNP-based heritability was derived from single nucleotide polymorphisms (SNPs).

RESULTS

Among all Amish individuals, additive genetic effects explained 11.1% to 36.6% of biomarker variances. estimates were consistently lower, ranging from 6.7% to 28.7%. The heritability of these biomarkers in subgroups of cognitively normal individuals and ε4 non-carriers yielded similar results.

DISCUSSION

Plasma biomarkers such as amyloid β, t-tau, and p-tau181 are moderately heritable in the Amish, underscoring the impact of genetic determinants of plasma biomarkers associated with AD.

摘要

引言

阿尔茨海默病（AD）的血浆生物标志物有望用于疾病诊断和预测，但其遗传基础仍未得到充分探索。

方法

我们测量了美国中西部阿米什人中血浆淀粉样蛋白β40（Aβ40）、Aβ42、Aβ42/Aβ40、总tau蛋白（t-tau）、磷酸化tau蛋白181（p-tau181）、Aβ42/t-tau、Aβ42/p-tau181、神经丝轻链和胶质纤维酸性蛋白。基于家系的遗传力是从多代家系中估计出来的，基于单核苷酸多态性（SNP）的遗传力是从单核苷酸多态性中推导出来的。